Although little is known about the physiologic role of Transforming Growth Factor (TGF)-b in vivo, immunohistochemical studies in the developing mouse embryo have implicated TGF-b in proliferation and differentiation of tissues in general especially the mesenchymally (bone, muscle, and blood vessels) and neural crest derived ones. Interestingly enough, intense staining is found in the craniofacial mesenchyme of neural crest origin, destined to become mandible, maxilla, palate, nose, and nasal sinuses. We have recently obtained cDNA probes for all 3 TGF-b subtypes (1,2 and 3) from Dr. Anita Roberts (NIH), and antibodies against the TGF-b1 and 2 are available commercially. We also have in our laboratory 12 human tumor cell lines originated from various neural tumors, ranging from conventional neuroblastoma, to peripheral primitive neuroectodermal tumors, to olfactory neuroblastoma. We will study the expression of TGF-b1, 2, and 3 in all these neural cell lines at the mRNA and protein level by Northern and Western blotting, and immunocytochemical staining by immunofluorescence. Various patterns of expression of these 3 TGF-b subtypes may be observed implicating a role of this growth factor in the neural childhood tumors. In addition, several possible emerging patterns of expression may further confirm our suspicion of different pathogenetic pathways in the development of these tumors, and finally may serve as differential markers in their diagnosis.